EU/3/00/008 - orphan designation for treatment of acute promyelocytic leukaemia

Arsenic trioxide

Overview

Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in March 2012 at the end of the period of market exclusivity.

On 18 October 2000, orphan designation EU/3/00/008 was granted by the European Commission to Voisin Consulting SARL, France, for arsenic trioxide for the treatment of acute promyelocytic leukaemia.

Arsenic trioxide has been authorised in the EU as Trisenox since 5 March 2002.

The sponsorship was transferred to Cell Therapeutics (UK) Ltd in 2001 and subsequently to Cephalon UK Limited, United Kingdom, in April 2006 and finally to Cephalon Europe, France, in June 2007.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

What is acute promyelocytic leukaemia?

Acute promyelocytic leukaemia is a disease in which cancer cells are found in the blood and the bone marrow. The bone marrow is the spongy tissue inside the large bones in the body. Normally, the bone marrow makes cells called 'blasts' that mature into several different types of blood cells that have specific functions in the body. These include red cells, white cells and platelets. Red blood cells carry oxygen and other materials to all tissues of the body. White blood cells fight infection. Platelets make the blood clot. When leukaemia develops, the bone marrow produces large numbers of abnormal blood cells. There are several types of leukaemias. In acute promyelocytic leukaemia blasts that are developing into white blood cells called myeloid cells are affected. The blasts do not mature and become too many. These blast cells are then found in the blood and also accumulate in the bone marrow. When the promyelocytic leukaemia develops quickly with many blasts it is defined as acute. Acute promyelocytic leukaemia is life-threatening.

What is the estimated number of patients affected by the condition?

At the time of designation, acute promyelocytic leukaemia affected not more than 0.8 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 30,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union. At the time of designation, this represented a population of 375,500,000 (Eurostat 2000).

What are the methods of treatment available?

Treatment for leukaemia is complex and depends on a number of factors including the type of leukaemia, the extent of the disease and whether the leukaemia has been treated before. It also depends on the patient's age, symptoms, and general health. Treatment of acute promyelocytic leukemia is chemotherapy (using drugs to kill cancer cells) and a vitamin-A-derived drug that helps the myeloid stem cells to mature into normal white blood cells.

Arsenic trioxide could be of potential significant benefit for the treatment of acute promyelocytic leukaemia. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicinal product expected to act?

It is not completely understood how arsenic trioxide works in the human body. The sponsor claims that arsenic trioxide breaks down the fundamental genetic material (DNA) of the cancer cells and thereby induces cell death.

What is the stage of development of this medicinal product?

The effects of arsenic trioxide have not been evaluated in experimental models. Clinical trials in patients with acute promyelocytic leukaemia were ongoing at the time of submission of the application for orphan designation.

Arsenic trioxide was not marketed or designated as orphan medicinal product elsewhere, at the time of submission.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 13 September 2000 a positive opinion recommending the grant of the above-mentioned designation.

Update: Arsenic trioxide (Trisenox) has been authorised in the European Union since 5 March 2002 for induction of remission and consolidation in adult patients with relapsed / refractory acute promyelocytic leukaemia (APL), characterised by the presence of the t(15;17) translocation and/or the presence of the pro-myelocytic leukaemia/retinoic-acid-receptor-alpha (PML/RAR-alpha) gene. Previous treatment should have included a retinoid and chemotherapy. The response rate of other acute myelogenous leukaemia subtypes to Trisenox has not been examined.

Opinions on orphan medicinal products designations are based on the following cumulative criteria

• the seriousness of the condition;
• the existence or not of alternative methods of diagnosis, prevention or treatment and;
• either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products, which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.

EU/3/00/008: Public summary of positive opinion for orphan designation of arsenic trioxide for the treatment of acute promyelocytic leukaemia

AdoptedReference Number: EMEA/COMP/9747/2003 Rev.4

Key facts

• Active substance:
  Arsenic trioxide
• Medicine name:
  Trisenox
• Intended use:
  Treatment of acute promyelocytic leukaemia
• Orphan designation status:
  Expired
• EU designation number:
  EU/3/00/008
• Date of designation:
  18/10/2000
• Sponsor:

  Cephalon Europe; 5 rue Charles Martigny; 94700 Maisons-Alfort Cedex; France; Tel. [phone]; Fax [phone]